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Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis

Giuseppe Nicastro1, María Flor García-Mayoral, David Hollingworth

  • 1Molecular Structure Division, Medical Research Council National Institute for Medical Research, London, UK.

Nature Structural & Molecular Biology
|November 13, 2012
PubMed

Insights

The KSRP protein

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Biochemistry

Background:

  • Let-7 microRNA (miRNA) functions as a tumor suppressor, regulating oncogenes and cellular processes.
  • The KSRP protein binds let-7 precursors, promoting mature let-7 processing and controlling cell proliferation, apoptosis, and differentiation.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying KSRP protein's specific binding to let-7 miRNA precursors.
  • To elucidate how the KSRP protein's KH3 domain recognizes and interacts with pre-let-7 RNA.

Main Methods:

  • Structural analysis of the KH3 domain-RNA complex.
  • Biochemical assays to assess binding specificity and functional impact.

Main Results:

  • The third KH domain (KH3) of KSRP specifically recognizes a G-rich sequence in the terminal loop of pre-let-7.
  • This KH3-RNA interaction dominates the binding and is crucial for KSRP's regulatory function.
  • The determined structure reveals the molecular basis for this noncanonical recognition.

Conclusions:

  • KSRP's selective binding to pre-let-7 is mediated by its KH3 domain recognizing a specific RNA motif.
  • This precise interaction is essential for KSRP's role in regulating let-7 maturation and cellular processes.
  • Understanding this interaction provides insights into miRNA biogenesis and tumor suppression.

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